The effects of tamoxifen on endometrial insulin-like growth factor-1 expression.
OBJECTIVE
To determine whether modulation of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 expression underlies the uterotropic effects associated with tamoxifen therapy in postmenopausal breast cancer patients.


METHODS
Using immunohistochemical techniques, we analyzed 37 endometrial specimens from biopsies (n = 18) or hysterectomies (n = 19) for Ki-67, insulin-like growth factor-1, and insulin-like growth factor-binding protein-1 expression. Specifically, five secretory- and three proliferative-phase endometrial specimens were used as controls; 20 specimens (including two endometrial adenocarcinomas) were analyzed from postmenopausal breast cancer patients treated with tamoxifen (20 mg/day) for at least 6 months; and nine endometrial adenocarcinoma specimens from patients not treated with tamoxifen were studied. Intensity of immunostaining was quantified using digitized imaging techniques.


RESULTS
Insulin-like growth factor-1 and insulin-like growth factor-1-binding protein-1 were found to be expressed in normal and neoplastic endometrium of all patients, regardless of tamoxifen treatment. However, insulin-like growth factor-1 expression varied cyclically in histologically normal endometrium, was reduced in undifferentiated endometrial tumors, and was upregulated in tamoxifen-treated specimens. Insulin-like growth factor-binding protein-1 immunostaining did not vary during the menstrual cycle, but it was reduced significantly in benign tamoxifen-exposed tissue and endometrial adenocarcinomas, regardless of degree of differentiation or tamoxifen exposure. No correlation was found between the expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 and the proliferative indices of the tissues examined.


CONCLUSIONS
The expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 in the uterus supports an autocrine and/or paracrine role for these proteins in endometrial physiology. Although further studies are needed, our investigation suggests that altered expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 may contribute to the uterotropic effects of tamoxifen.
Elkas
J
J
Division of Obstetrics at the National Naval Medical Center, Bethesda, Maryland, USA.
Gray
K
K
Howard
L
L
Petit
N
N
Pohl
J
J
Armstrong
A
A
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000473:pathology; D004717:Endometrium / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis; D016037:Single-Blind Method; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D018970:Insulin-Like Growth Factor Binding Protein 1; D019394:Ki-67 Antigen; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I